1. Chromosomes and Gene Expression
  2. Genetics and Genomics
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Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins

  1. Matthew WK Wong
  2. Anbupalam Thalamuthu
  3. Nady Braidy
  4. Karen A Mather
  5. Yue Liu
  6. Liliana Ciobanu
  7. Bernhardt T Baune
  8. Nicola J Armstrong
  9. John Kwok
  10. Peter Schofield
  11. Margaret J Wright
  12. David Ames
  13. Russell Pickford
  14. Teresa Lee
  15. Anne Poljak
  16. Perminder S Sachdev  Is a corresponding author
  1. Centre for Healthy Brain Ageing, University of New South Wales, Australia
  2. The University of Adelaide, Adelaide Medical School, Discipline of Psychiatry, Australia
  3. Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Australia
  4. Mathematics and Statistics, Murdoch University, Australia
  5. Brain and Mind Centre, The University of Sydney, Australia
  6. Neuroscience Research Australia, Australia
  7. Queensland Brain Institute, University of Queensland, Australia
  8. University of Melbourne Academic Unit for Psychiatry of Old Age, St George's Hospital, Australia
  9. University of New South Wales, Australia
Research Article
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Cite this article as: eLife 2020;9:e58954 doi: 10.7554/eLife.58954

Abstract

The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins Study (OATS) and explored corresponding gene expression and DNA methylation associations. 27/209 lipids (13.3%) detected by liquid chromatography-coupled mass spectrometry (LC-MS) were significantly heritable under the classical ACE twin model (h2=0.28-0.59), which included ceramides (Cer) and triglycerides (TG). Relative to non-significantly heritable TGs, heritable TGs had a greater number of associations with gene transcripts, not directly associated with lipid metabolism, but with immune function, signalling and transcriptional regulation. Genome-wide average DNA methylation (GWAM) levels accounted for variability in some non-heritable lipids. We reveal a complex interplay of genetic and environmental influences on the ageing plasma lipidome.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

The following previously published data sets were used

Article and author information

Author details

  1. Matthew WK Wong

    School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Anbupalam Thalamuthu

    School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Nady Braidy

    School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Karen A Mather

    School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Yue Liu

    School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Liliana Ciobanu

    Adelaide Medical School, The University of Adelaide, Adelaide Medical School, Discipline of Psychiatry, Adelaide, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Bernhardt T Baune

    Department of Psychiatry, Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Nicola J Armstrong

    Mathematics and Statistics, Mathematics and Statistics, Murdoch University, Perth, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4477-293X
  9. John Kwok

    Brain and Mind Centre, Brain and Mind Centre, The University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  10. Peter Schofield

    Faculty of Medicine, Neuroscience Research Australia, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  11. Margaret J Wright

    Queensland Brain Institute, Queensland Brain Institute, University of Queensland, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7133-4970
  12. David Ames

    Academic Unit for Psychiatry of Old Age, University of Melbourne Academic Unit for Psychiatry of Old Age, St George's Hospital, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  13. Russell Pickford

    Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  14. Teresa Lee

    School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  15. Anne Poljak

    School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  16. Perminder S Sachdev

    School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia
    For correspondence
    p.sachdev@unsw.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9595-3220

Funding

National Health and Medical Research Council

  • Nady Braidy
  • Perminder S Sachdev

Australian Research Council

  • Nady Braidy

Rebecca L. Cooper Medical Research Foundation

  • Nady Braidy
  • Anne Poljak
  • Perminder S Sachdev

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: OATS was approved by the Ethics Committees of the University of New South Wales and the South Eastern Sydney Local Health District (ethics approval HC17414). All work involving human participants was performed in accordance with the principles of the Declaration of Helsinki of the World Medical Association. Informed consent was obtained from all participants and/or guardians.

Reviewing Editor

  1. Mone Zaidi, Icahn School of Medicine at Mount Sinai, United States

Publication history

  1. Received: May 18, 2020
  2. Accepted: July 20, 2020
  3. Accepted Manuscript published: July 22, 2020 (version 1)
  4. Version of Record published: July 31, 2020 (version 2)

Copyright

© 2020, Wong et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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